The intent of this K26 Mid Career Investigator proposal is twofold. First, it will provide the means to support and mentor trainees in the field of mouse pathobiology. Second, it will provide the PI, Caroline Zeiss, with the means to consolidate her research effort in the area of retinal degeneration. Caroline Zeiss is a practicing veterinary pathologist conducting independently funded research (most recently via a successful R21 proposal) in the area of retinal degeneration. In addition, she developed and directs the Mouse Pathologic Phenotyping Core at Yale University School of Medicine as well as its now fully operational Metabolic Phenotyping Core. She developed and directs the Section of Comparative Medicine's only graduate course, and more recently, has developed a new Laboratory Animal Pathology course. These new resources, together with those already available within the Section, will provide the basis for a formal training syllabus in mouse pathobiology in accordance with that recently proposed by the Mouse Pathologist's Consortium. This scientific basis of this proposal is to develop murine models for age-related macular degeneration (AMD), and represents the continuation of the PI's established research field. The first aim of the original proposal has been completed. Therefore this resubmission focuses whether polymorphisms in two recently discovered genes (CFH and HTRA1) that are associated with AMD in humans can induce the disease in mice. Further, additional vision research laboratories have been included as collaborators, thus providing the trainee a choice of laboratories in which to obtain research experience. Under guidance of Dr. Zeiss, trainees will obtain didactic and hands-on experience in mouse pathology, and will complete a mentored research project aimed at generating a publication. The need for comparative pathologists trained in pathobiologic principles has been evident for several years now. This need has provided the impetus for development of organizations such as the ACVP/STP Coalition for Veterinary Pathology Fellows. Support of this proposal would provide opportunities for trainees with experience in veterinary pathology to gain broad experience in comparative mouse pathology and phenotyping as well in research methodology. PUBLIC HEALTH RELEVANCE (provided by applicant): The purpose of this K26 award entitled Complex mouse models of age-related macular degeneration is twofold. First, it will provide the means to support and mentor trainees in the field of mouse pathobiology. Second, it will provide the PI, Caroline Zeiss, with the means to consolidate her research effort in the area of retinal degeneration. The award spans three years, and its successful funding will support one trainee per year, and provide protected time for the PI to consolidate her lab and establish solid research support.